Fas (CD95, Apo-1) is a constitutively expressed member of the tumor necrosis factor (TNF) receptor super family of death receptors that shares a conserved 80 amino acid death domain in their cytoplasmic tail which is critical in apoptosis signaling. Upon ligation of Fas, the sequential association of FADD and pro forms of caspase 8 or 10 leads to the formation of the death inducing signaling complex (DISC) resulting in activation of caspase 8 or 10 and execution of apoptosis.
Fas can be post-translationally modified in a redox-dependent manner via the covalent attachment of the small antioxidant tripeptide, glutathione (GSH). This post-translational modification is known as protein S-glutathionylation. S-glutathionylation of cysteine 294 in the endodomain of murine Fas (Fas-SSG) can be sustained via caspase-dependent degradation of the de-glutathionylating enzyme, glutaredoxin-1 (Grx1). Fas-SSG may be functionally important as it enhances recruitment Fas into lipid rafts, promotes FasL binding, DISC formation, and caspase activation thereby amplifying cell death. However, despite these novel observations, the early events that mediate S-glutathionylation of Fas remain unknown.